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Research of experimental pathology on the model for ulcerative colitis - large bowel cancer

Research Project

Project/Area Number 04670202
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionGifu University

Principal Investigator

MORI Hideki  Gifu University School of Medicine, Department of Pathology, Professor, 医学部, 教授 (70021433)

Co-Investigator(Kenkyū-buntansha) SUGIE Shigeyuki  Hospital associated with Gifu University School of Medicine, Department of Patho, 医学部・附属病院, 助手 (60187648)
YOSHIMI Naoki  Gifu University School of Medicine, Department of Pathology, Instructor, 医学部, 講師 (30166996)
TANAKA Takuji  Gifu University School of Medicine, Department of Pathology, Associate professor, 医学部, 助教授 (40126743)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsHydroxyanthraquinone / Ulcerative colitis / Large bowel cancer / Rat / Mouse / Cell proliferation / Tumor promotion / Cytokines / 1.2-dimethylhydrazine / 結腸腫瘍 / 肛門腫瘍 / ハムスター / BrdU / 大腸粘膜 / ODC活性 / 陰高長 / 潰瘍性病変 / メラノーシス
Research Abstract

1) Development of the model for ulcerative colitis - large bowel cancer : Dietary administration of l-hydroxyanthraquinone (HA*) (1%) to rats for approximately 460 days was done. Twenty five rats out of 29 effective animals developed large bowel neoplasms (adenoma or adenocarcinoma). All of these effective rats also developed some pathological changes which are often seen in ulcerative colitis patients. They were crypt abscess, melanosis, erosion or regenerative epithels. These results indicate that HA* induces simultaneously pathological changes resembling those appeared in the case of ulcerative colitis and neoplasms.
2) Cell kinetic analysis of proliferative epithelial cells in rats given HA* : Sequential observation of the large bowels of rats exposed to HA* (1%) by sacrifice of animals at 4, 8 or 12 months after the start of tye dietary exposure. Thickness, number of cells constituting crypt, labelling indices of BrdU in the crypt cells, ODC activity and appearance of the changes s … More uch as erosion, crypt abscess of the large bowels of rats with HA* were respectively greater than those of control animals. Each of the biomarkers became greater responding to the exposure-time of HA*.
3) Tumor-promotive effect of 1, 8-dihydroxianthraquinone (danthron) in the large of mice : Modifying effect of danthron on dimethylhydrazine (DMH)-induced large bowel carcinogenesis in mice was examined. Incidence of colon neoplasms (adenoma or adenocarcinoma) in mice given DMH together with danthron was significantly higher than that of mice exposed to DMH alone. ODC activity of the large bowel of mice given danthron was much greater than that of controls.
Expression of cytokines, TNF-a and IL-la in the large bowel carcinogenesis by MAM acetate and HA* : Expression of the cytokines was examined by RT-PCR method. Expression of the cytokines in the colon neoplasms was stronger than in non-neoplastic mucosa. That of cytokines in the colon mucosa given both agents or either of the agents was aloso greater than in controls. The synergistic effects of HA* with MAM acetate might be related to the biological effects of the cytokines expressed in the inflammatory conditioned generated by HA*. Less

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Mori,Y.,Yoshimi,N.,Iwata,H.,Tanaka,T.,Mori,H.: "The synergistic effect of l-hydroxyanthraquinone on methylazoxymethanol acetate-induced carcinogenesis in rats" Carcinogenesis. 12. 335-338 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori,H.,Mori,Y.,Tanaka,T.,Yoshimi,N.,Sugie,S.,Kawamori,T.,Narisawa,T.: "Cell kinetic analysis of the mucosal epithelium and assay of ornithine decarboxylase activity during the process of l-hydroxyanthraquinone-induced large bowel carcinogenesis" Carcinogenesis. 13. 2217-2220 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori,H.,Morishita,Y.,Mori,Y.,Yoshimi,N.,Sugie,S.,Tanaka,T.: "Effect of magnesium hydroxide on methylazoxymethanol-acetate-induced epithelial proliferation in the large bowels of rats" Cancer Letters. 61. 43-48 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tanaka,T.,Kojima,T.,Suzui,M.,Mori,H.: "Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid:suppressing effects on tumor development and biomarkers expression of colon tumorigenesis" Cancer Research. 53. 3908-3913 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Wang,A.,Yoshimi,N.,Tanaka,T.,Mori,H.: "Inhibitory effects of magnesium hydrpxide on c-myc expression and cell proliferation induced by methylazoxymethanol acetate in rat colon" Cancer Letters. 75. 73-78 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yoshimi,N.,Sato,S.,Makita,H.,Wang,A.,Hirose,Y.,Tanaka,T.,Mori,H.: "Expression of cytokines,TNF-a and IL-la,in MAM acetate and l-hydroxyanthraquinone-induced colon carcinogenesis of rats" Carcinogenesis. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori,H.: "Genotoxicity of naturally occurring metabolites;Structural analogs of aflatoxin and related chemicals.In“Applied Mycology 5"" Marcel Dekker Inc.,N.Y./Basel, 231-253 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori,H.,Morishita,Y.,Shinoda,T.,Tanaka,T.: "Preventive effect of magnesium hydroxide on carcinogen-induced large bowle carcinogenesis in rats.In “Antimutagenesis and anticarcinogenesis III"" Plenum Publ.Corp., 111-118 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori, Y., Yoshimi, N., Iwata, H., Tanaka, T., Mori, H.: "The synergistic effect of l-hydroxyanthraquinone on methylazoxymethanol acetate-induced carcinogenesis in rats." Carcinogenesis. 12. 335-338 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori, H., Mori, Y., Tanaka, T., Yoshimi, N., Sugie, S., Kawamori, T., Narisawa, T.: "Cell kinetic analysis of the mucosal epithelium and assay of ornithine decarboxylase activity during the process of l-hydroxyanthraquonone-induced large bowel carcinogenesis in rats." Carcinogenesis. 13. 2217-2220 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori, H., Morishita, Y., Mori, Y., Yoshimi, N., Sugie, S., Tanaka, T.: "Effect of magnesium hydroxide on methylazoxymathanol acetate-induced epithelial proliferation in the large bowels of rats." Cancer Lett.61. 43-48 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tanaka, T., Kojima, T., Suzui, M., Mori, H.: "Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid ; supprressing effects on tumor development and bionarkers expression of colon tumorigenesis." Cancer Res.53. 3908-3913 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Wang, A., Yoshimi, N., Tanaka, T., Mori, H.: "Inhibitory effects of magnesium hydroxide on c-myc expression and cell proliferation induced by methylazoxymethanol acetate in rat colon." Cancer Lett.75. 73-78 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori, H., Kawamori, T., Tanaka, T., Ohnishi, M., Yamahara, J.: "Chemopreventive effect of costunolide, a costituent of oriental medicine on azoxymethane-induced intestinal carcinogenesis in rats." Cancer Lett.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yoshimi, N., Sato, S., Makita, H.Wang, A., Hirose, Y., Tanaka, T., Mori, H.: "Expression of cytokines, TNF-a and IL-la, in MAM acetate and l-hydroxyanthraquinone-induced colon carcinogenesis of rats." Carcinogenesis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori, H.: Genotoxicity of naturally occurring metabolites ; structural analogs of aflatoxin and related chemicals.In "Applied Mycology" 5 ; Mycotoxins in Ecological Systems.Marcel Dekker Inc., N.Y./Basel, 231-253 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori, H., Morishita, Y., Shinoda, T., Tanaka, T.: Preventive effect of magnesium hydroxide on carcinogen-induced large bowel carcinogenesis in rats.In "Antimutagenesis and Anticarcinogenesis III". Plenum Publ.Corp., 111-118 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori,H.,Tanaka,T.: "Chemopreventive retinoids" Drugs of the future. 18. 737-742 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka,T.,Kojima,T.,Suzui,M.,Mori,H.: "Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid:Suppressing effects on tumor development and biomarkers expression of colon carcinogenesis" Cancer Research. 53. 3908-3913 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kojima,A.,Tanaka,T.,Kawamori,T.,Hara,A.,Mori,H.: "Chemopreventive effects of dietary D,L-α-difluoromethylornithine,an ornithine decarboxylase inhibitor;on initiation and postinitiation stages of diethylnitrosamine-induced rat hepatocarcinogenesis" Cancer Research. 53. 3903-3907 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka,T.,Morishita,Y.,Kawamori,T.,Suzui,M.,Kojima,T.,Sugie,S.,Mori,H.: "synergistic effect of radiation on colon carcinogenesis induced by methylazoxymethanol acetate in ACI/N rats" Jpn.J.Cancer Res.84. 1031-1036 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugie,S.,Okumura,A.,Tanaka,T.,Mori,H.: "Inhibitory effects of benzyl isothiocyanate and benzyl thiocyanate on diethylnitrosamine-induced hepatocarcinogenesis in rats" Jpn.J.Cancer Res.84. 865-870 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wang,A.,Yoshimi,N.,Tanaka,T.,Mori,H.: "Inhibitory effects of magnesium hydroxide on c-myc expression and cell proliferation induced by methylazoxymetahnol acetate in rat colon" Cancer Letters. 75. 73-78 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kawai,K.,Hisada,K.,Mori,H.,Nozawa,Y: "Molecular approach to the toxic action of quinone mycotoxins-chemical structure and biochemistry in“Current Topics in Medical Mycology"ed by M.Borgers,R.Hay,M.Rinaldi" Springer-Verlag, 207-230 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mori,H.,Morishita,Y.,Shinoda,T.,Tanaka,T.: "Preventive effects of magnesium hydroxide on carcinogen-in-duced large bowel carcinogenesis in rats.in“Antimutagenesis and Anticarcinogenesis"ed by Hayatus,K.et al." Plenum Publ., 111-118 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mori,H., Morishita,Y., Mori,Y., Yoshimi,N., Sugie,S., Tanaka,T.: "Effect of magnesium hydroxide on methylazoxymethanol-induced epithelial proliferation in the large bowels of rat" Cancer Letters. 61. 43-89 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mori,H., Morishita,Y., Tanaka,T., Okumu-ra,A., Wang,A.: "Effect of magensium hydroxide on the cell cycle of muco-sal epithelium; A mechanism of the suppressive action onthe carcinogen-induced large bowel carcinogenesis in rats" Journal of Japanese Society of Magnesium Research. 11. 93-101 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mori,H., Morishita,Y., Sugie,S., Tanaka,T., Kojima,T., Suzui,M.: "Carcinogenicity of examination of 1-nitropyrene oxides and related chemicals; Lack of their tumorigenic effects in a newborn mice assay" Journal of Toxicological Sciences. 17. 235-241 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mori,H., Yoshimi,N., Sugie,S., Tanaka,T., Morshita,Y., Jinlog: "Inhibitory effect of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel synthesized retinoid on azoxy-methane-induced intestinal carcinogenesis in rats" Cancer Letters. 66. 93-98 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mori,H., Mori,Y., Tanaka,T., Yoshimi,N., Sugie,S., Kawamori: "Cell kinetic analysis of the mucosal epithelium and ass-ay of ornithine decarboxylase activity during the pro-cess of 1-hydroxyanthraquinone-induced large bowel carci" Carcinogenesis. 13. (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sugie,S., Yoshimi,N., Okumura,A., Tanaka,T., Mori,H.: "Modifying effects of benzyl isothiocyanate on DNA synthe-sis in primary culture of rat hepatocytes: a possible assay for chemopreventive agents" Carcinogenesis. 14. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mori,H.: "Genotoxicity of naturally occurring metabolites; Structu-ral analogs of aflatoxin and related chemicals in″Applied Mycology 5; eds by D. Bhatnager et al.″" Marcel Dekker Inc., New York/Basel, 231-253 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mori,H., Morishita,Y., Shinoda,T., Tanaka,T.: "Preventive effect of magnesium hydroxide on carcinogen-induced large bowel carcinogenesis in rats. in″Antimuta-genesis and Anticarcinogenesis Mechanism III″" Prenum Press, (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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